The objective of this proposed study is to define the basic biochemical events following the acute and chronic effects of opiates and opioid peptides in homogeneous neurotumor cell lines which express opiate receptors. It is hoped to define the pharmacology of the effects of opiate agonists in terms of specific biochemical changes in the composition of neural cell membranes. Biochemical studies will be aimed at relating the initial inhibitory effects on adenylate cyclase with glycosyltransferase activities and the synthesis of specific glycolipids (gangliosides) and glycoproteins. The functional consequences of changes in neural cell complex carbohydrate composition will then be assessed in terms of alterations in membrane potential and ion permeability. By combining all these approaches, it is hoped that we will begin to understand the mechanisms of acute opiate action, opiate addiction, tolerance and withdrawal and gain insights into the role of the endogenous opioids, the enkephalins and endorphins.